ERC Starting Grant for Roxanne Kieltyka: stem cells in gels

Chemist Roxanne Kieltyka has received an ERC Starting Grant of 2 million euros. In her lab, she creates gels that mimic the instructive material that supports cells in our body. With the grant, she aims to make these gels stiff and tough, and to create a bio-printed miniature heart ventricle.

Gels that can heal themselves

Kieltyka works in the area of supramolecular chemistry that involves creating large, ordered structures out of small molecules. These molecules self-assemble through non-covalent bonds – such as hydrogen bonding – to form polymeric structures and eventually, gel-phase materials. Due to the inherent dynamic nature of the interactions that hold them together, this class of materials can have remarkable properties. For example, they can respond to their environment and show self-healing behaviour. ‘Both their structure and capacity to provide biological signals make them perfect for mimicking the natural extracellular matrix, a biological material that behaves as an instructive scaffold for cells in the body,’ Kieltyka says.

A squaramide

The art of design

To make such materials, Kieltyka designs the molecular building blocks, also called monomers, in a specific way. ‘We endow the monomers with specific molecular units that are primed to interact with each other through non-covalent interactions and to trigger their stacking into polymers – long chains of monomers.’ More specifically, Kieltyka uses squaramides as building blocks – a class of flat, square-like compounds that have four carbon atoms at their core. On each corner, an oxygen or nitrogen atom enable hydrogen bonding of the squaramide motif to occur, triggering their assembly in a head-to-tail manner into polymeric materials, eventually forming a gel.

Seeding stem cells within the gel

These gels can then be used to investigate and direct cellular behaviour by providing biophysical and biochemical signals. Kieltyka seeds induced pluripotent stem cells (iPSCs) within the gels, a class of cells that can become virtually any type of cell through a process called differentiating. This makes it possible to engineer a range of artificial tissues. ‘So far we have used the self-recovery property of the material to culture iPSCs within the gels. It’s even possible to release the cells from the material in a gentle manner, so we can analyze them afterwards for subsequent applications,’ she says.

Making stiffer gels

However, there is one drawback: the gels Kieltyka currently makes are much softer than a wide range of adult tissues. The ERC Starting Grant will provide Kieltyka with the opportunity to devise new chemical strategies to overcome this problem. ‘We will synthesize new supramolecular polymer materials with a range of reactive groups whose reaction rate can be tailored to control stiffening of these gels in space and time.’ Her ultimate goal is to use these materials to 3D bioprint a miniature heart ventricle embedded with heart cells made from induced pluripotent stem cells. This miniature heart model can be used for drug testing applications and to better understand diseased heart tissue.

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